Surgeons Remove Rare 8.4 cm Silent Adrenal Cancer in 40-Year-Old Woman

A dull ache in the left flank that had persisted for three months turned out to be something far more serious than a muscle strain for one 40-year-old woman. When she arrived at a urology outpatient department, she had no weight loss, no hypertension, no palpitations, no blood in her urine, and no constitutional symptoms of any kind. Her only complaint was a non-radiating, dull pain on the left side, and her physical examination showed nothing more than mild tenderness in the same region. There was no palpable mass and no other abnormality to find. Yet the imaging that followed would reveal one of the rarest malignancies in human medicine, growing silently above her left kidney, and a clinical journey that illustrates just how difficult diagnosis and treatment of this disease can be.

An ultrasound of the abdomen and pelvis was the first test to raise the alarm. It showed a heterogeneous left suprarenal mass measuring approximately 7.6 by 5.1 centimeters, appearing hypoechoic with mixed echogenicity and apparently arising from the upper pole of the left kidney. Importantly, there was no hydronephrosis and no renal calculi, which helped steer the diagnostic workup away from straightforward kidney pathology and toward the adrenal gland. The finding placed the patient squarely in the category that endocrine and urologic surgeons watch most carefully: a large, unilateral adrenal mass in a middle-aged adult, large enough that malignancy becomes the leading suspicion even in the complete absence of hormone excess.

The clinical team recognized that the differential diagnosis for a mass of this size had to span both primary adrenal diseases and secondary lesions. Adrenocortical carcinoma was the primary suspicion, since any unilateral adrenal mass greater than four to six centimeters demands that consideration, and non-functional variants often present late with exactly this kind of local symptom. A non-functioning adrenocortical adenoma was also on the list; although these benign tumors are typically smaller than four centimeters and characterized by high lipid content on imaging, large macroadenomas can occur, and only aggressive histopathologic features could rule one out definitively after surgery. Pheochromocytoma, the so-called 10 percent tumor, had to be excluded with plasma or urinary metanephrines before any operation, because missing it risks a catastrophic intraoperative hypertensive crisis even in patients without classic paroxysms. Adrenal metastasis was another possibility, since the adrenal glands are common sites for secondary spread from cancers of the lung, breast, kidney, and melanoma. Benign lesions completed the list, including adrenal myelolipoma, which is composed of mature adipose tissue and hematopoietic elements and can grow quite large but usually shows characteristic fat density on CT, and ganglioneuroma, a rare benign tumor of neural crest origin that is typically slow-growing, non-functional, and capable of reaching significant sizes in younger adults.

A contrast-enhanced CT scan of the abdomen and pelvis sharpened the picture considerably. It demonstrated a well-defined heterogeneous left adrenal mass measuring 8.4 by 7.6 by 6.5 centimeters, with heterogeneous post-contrast enhancement and clearly visible necrotic areas. Those radiologic features matter because tumor heterogeneity and necrosis are among the findings that raise suspicion for malignancy in adrenal masses. The mass abutted the spleen, the tail of the pancreas, the upper pole of the left kidney, and the left diaphragmatic crus, but without definite invasion of adjacent organs. No calcification, regional lymphadenopathy, or distant lesions were identified, which meant the tumor appeared localized and therefore potentially curable by resection, the only approach with curative potential in localized disease.

Before any operation could proceed, the team needed to prove the tumor was hormonally silent. A complete functional adrenal evaluation was performed, including serum metanephrines, normetanephrines, 24-hour urinary cortisol, and the aldosterone-renin ratio, and every value came back within normal limits. Urine free cortisol measured 23.1 micrograms per day against a reference range of 4.6 to 28.6, plasma free normetanephrine was 128.46 picograms per milliliter within a range of zero to 190, and the aldosterone to direct renin ratio was 9.5, all unremarkable. Baseline laboratory investigations were equally normal. This functional workup is not a formality; it is the step that excludes pheochromocytoma and functioning adrenocortical pathology and determines how safely a patient can be carried through anesthesia and surgery.

Following a multidisciplinary team discussion, the patient was optimized for surgery and underwent a left open adrenalectomy under general anesthesia, performed through a left hemichevron incision with the patient in the supine position. The operation was uneventful, and the mass was excised completely. The choice of an open approach was deliberate and reflects current best practice for large or potentially invasive adrenal tumors, because open surgery offers improved margin control and reduces the risk of intraoperative tumor spillage. In this case, the open technique allowed complete removal with negative margins and minimal morbidity, exactly the result that curative intent demands.

The gross specimen and the histopathology that followed told the true story of what the imaging could only suggest. Microscopic examination revealed an adrenocortical neoplasm composed of pleomorphic polygonal cells with eosinophilic to clear cytoplasm. The mitotic activity exceeded five mitoses per 50 high-power fields, atypical mitoses were present, and tumor necrosis was identified. Lymphovascular invasion was found, and the tumor was seen invading periadrenal adipose tissue, consistent with pT3 disease. The surgical margins were free, with the lesion sitting just 0.1 centimeters from the inked margin. The Modified Weiss score, a histopathologic scoring system used to confirm diagnosis and guide prognosis, came back at 6, indicating malignant behavior and confirming the diagnosis of adrenocortical carcinoma.

The diagnosis rests on a broader toolkit than the Weiss criteria alone. Research on the diagnostic and prognostic assessment of adrenocortical carcinomas by pathological features, immunohistochemical markers, and reticular histochemical staining has shown that six immunohistochemical antibodies, namely MelanA, Ki-67, IGF-2, beta-catenin, P53, and CYP11B1, together with alterations in the reticulin framework, carry diagnostic value. Among these, Ki-67 and reticulin staining have been the most recommended. Evident reticulin staining was frequently present in adrenocortical carcinomas with high statistical significance, and Ki-67 was significantly higher in carcinomas than in their benign counterparts, with both differences reported at p less than 0.001. These markers help pathologists separate aggressive carcinomas from large benign adenomas, a distinction that confirms diagnosis and guides prognosis.

After the operation, the patient was reviewed again by the urology multidisciplinary team, which reached a consensus to maintain strict surveillance with regular follow-up because of the malignant potential of the tumor. Her first follow-up visit at three months included relevant laboratory tests and a CT scan of the abdomen and pelvis, which showed no evidence of local recurrence or systemic metastasis. That early result is encouraging, but the team knows the statistics. Recurrence rates for adrenocortical carcinoma reach up to 70 percent within two years, which is why long-term follow-up will be necessary and why the surveillance plan was framed as strict rather than routine.

The case also highlights an unresolved controversy in adjuvant therapy. Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features, such as tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage. However, a 13-institution study by the US Adrenocortical Carcinoma Group on outcomes of adjuvant mitotane after resection found that adjuvant mitotane was not associated with improved recurrence-free survival or overall survival, leaving clinicians without a clearly proven systemic option in the adjuvant setting. Against that backdrop, the fundamentals of this case stand out. Adrenocortical carcinoma comprises less than 0.2 percent of all malignancies, with an annual incidence of 0.7 to 2 per million, and many tumors present incidentally on imaging for unrelated causes because their symptoms are vague or absent. Management is challenged by the rarity of the disease, inhomogeneity in presentation, and limited systemic therapies. This patient’s story demonstrates that early identification of a large non-functional adrenal mass suspicious for malignancy, prompt surgical resection through an open approach when size and invasion risk warrant it, accurate histopathologic assessment with the Modified Weiss criteria, and organized multidisciplinary postoperative surveillance can together deliver a complete resection with negative margins and a recurrence-free first three months, even in a tumor with aggressive histopathologic features.

Subject of Research: Adrenalectomy for a Large Non‐Functional Adrenocortical Tumor With Aggressive Histopathologic Features: A Clinical Case Report

Article Title: Adrenalectomy for a Large Non‐Functional Adrenocortical Tumor With Aggressive Histopathologic Features: A Clinical Case Report

Article References: Khan, J., Asif, A. E., Yousaf, H., Nawaz, H. A., Hassaan, M., Rahim, S., Yeasmin, F., Khalid, M., & Segawa, F. (2026). Adrenalectomy for a Large Non‐Functional Adrenocortical Tumor With Aggressive Histopathologic Features: A Clinical Case Report. Clinical Case Reports, 14(11), Article e73740. https://doi.org/10.1002/ccr3.73740

Image Credits: AI Generated

DOI: 10.1002/ccr3.73740

Keywords: Adrenalectomy, Large, Functional, Adrenocortical, Tumor, Aggressive, Histopathologic, Features, Clinical, Case, Report, scientific research